In previous studies we have described various aspects of adenylate cyclase, its dispersion, chromatographic behavior, kinetics with respect to metal and metal-ATP, stimulation and inhibition by adenosine, stimulation by NAD and by vanadate, and the influence on its assay of nucleotide pyrophosphatase and components of ATP-regenerating systems. We have developed improved methods for assaying activity and an enzymatic procedure for preparing labeled substrate. Our immediate objectives in the proposed studies are to: a) purify those components of the cyclase system necessary for the evaluation of phosphorylation/dephosphorylation control of activity, specifically by fluoride and vanadate; b) to establish relationships involved in the Mn-facilitated redox control of fluoride- and glucagon-stimulated liver cyclase activities; and c) to continue to develop larger scale purification techniques for adenylate cyclases from brain and liver.